Design, synthesis and SAR studies of novel 1,2-bis(aminomethyl)cyclohexane platinum(II) complexes with cytotoxic activity. Studies of interaction with DNA of iodinated seven-membered 1,4-diaminoplatinocycles

Gay, Marina; Montaña, Ángel M.; Batalla, Consuelo; Mesas, Juan M.; Alegre, M. Teresa

doi:10.1016/j.jinorgbio.2014.09.012

Cited by 16 publications

(3 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oxygen-binding hemerythrin (O 2 -binding Hr) homologs were identified based on the statistical significance of aligning O 2 -binding Hr sequences from two annelid species, Phascolopsis gouldii [ 13 ] and Themiste hennahi [ 14 ], with non-mutated protein sequences annotated as hemerythrin or hemerythrin-like proteins in the PDB. The sequences of two O 2 -binding Hrs, from the proteobacteria Methylococcus capsulatus [ 15 ] and Desulfovibrio vulgaris [ 16 ], were statistically similar to the annelid sequences ( Table 1 ), and were used as queries in subsequent sequence similarity searches. In contrast, the N-terminal domain of the human F-box and leucine-rich repeat protein 5 (FBXL5), which possess an iron-coordination site that does not bind oxygen [ 17 – 19 ], was not significantly similar to any of the annelid hemerythrin sequences used here as reference ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Molecular Evolution of the Oxygen-Binding Hemerythrin Domain

2016

View full text Add to dashboard Cite

BackgroundThe evolution of oxygenic photosynthesis during Precambrian times entailed the diversification of strategies minimizing reactive oxygen species-associated damage. Four families of oxygen-carrier proteins (hemoglobin, hemerythrin and the two non-homologous families of arthropodan and molluscan hemocyanins) are known to have evolved independently the capacity to bind oxygen reversibly, providing cells with strategies to cope with the evolutionary pressure of oxygen accumulation. Oxygen-binding hemerythrin was first studied in marine invertebrates but further research has made it clear that it is present in the three domains of life, strongly suggesting that its origin predated the emergence of eukaryotes.ResultsOxygen-binding hemerythrins are a monophyletic sub-group of the hemerythrin/HHE (histidine, histidine, glutamic acid) cation-binding domain. Oxygen-binding hemerythrin homologs were unambiguously identified in 367/2236 bacterial, 21/150 archaeal and 4/135 eukaryotic genomes. Overall, oxygen-binding hemerythrin homologues were found in the same proportion as single-domain and as long protein sequences. The associated functions of protein domains in long hemerythrin sequences can be classified in three major groups: signal transduction, phosphorelay response regulation, and protein binding. This suggests that in many organisms the reversible oxygen-binding capacity was incorporated in signaling pathways. A maximum-likelihood tree of oxygen-binding hemerythrin homologues revealed a complex evolutionary history in which lateral gene transfer, duplications and gene losses appear to have played an important role.ConclusionsHemerythrin is an ancient protein domain with a complex evolutionary history. The distinctive iron-binding coordination site of oxygen-binding hemerythrins evolved first in prokaryotes, very likely prior to the divergence of Firmicutes and Proteobacteria, and spread into many bacterial, archaeal and eukaryotic species. The later evolution of the oxygen-binding hemerythrin domain in both prokaryotes and eukaryotes led to a wide variety of functions, ranging from protection against oxidative damage in anaerobic and microaerophilic organisms, to oxygen supplying to particular enzymes and pathways in aerobic and facultative species.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular Evolution of the Oxygen-Binding Hemerythrin Domain

2016

View full text Add to dashboard Cite

show abstract

“…It has been indicated that the glutathione (GSH) level in cancerous cells is up to 1-11 mM, which is considerably higher than that in normal cells as well as in the extracellular fluid and blood. Therefore, a relatively strong reducing environment in tumor cells could be a promising biosignal for smart drug delivery [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Glucosamine-Modified Reduction-Responsive Polymeric Micelles for Liver Cancer Therapy

Liu

et al. 2023

Molecules

View full text Add to dashboard Cite

In this work, glucose transporter-1 (GLUT-1) and glutathione (GSH) over-expression in liver cancer was utilized to design a reduction-responsive and active targeting drug delivery system AG-PEG-SS-PCL (APSP) for the delivery of sorafenib (SF). The SF-APSP micelles were prepared using the thin film hydration method and characterized by various techniques. In vitro release experiments showed that the cumulative release of SF-APSP micelles in the simulated tumor microenvironment (pH 7.4 with GSH) reached 94.76 ± 1.78% at 48 h, while it was only 20.32 ± 1.67% in the normal physiological environment (pH 7.4 without GSH). The in vitro study revealed that glucosamine (AG) enhanced the antitumor effects of SF, and SF-APSP micelles inhibited proliferation by targeting HepG2 cells and suppressing cyclin D1 expression. The in vivo antitumor efficacy study further confirmed that the SF-APSP micelles had excellent antitumor effects and better tolerance against nude mouse with HepG2 cells than other treatment groups. All in all, these results indicated that SF-APSP micelles could be a promising drug delivery system for anti-hepatoma treatment.

show abstract

“…Αντιθέτως, η υποκατάσταση με αλογόνα ή αλκυλομάδες στην 3΄ θέση της αρυλαμίνης (R 1 = Cl, Br, I, -CH3, -CH2CH3) έδωσε παράγωγα με αυξημένη δραστικότητα και διευρυμένο φάσμα δράσης σε καρκινικές σειρές Μια ιδιαίτερη κατηγορία με έντονο κλινικό ενδιαφέρον αποτελούν τα ραδιοφάρμακα, τα οποία είναι ραδιοϊσότοπα που χρησιμοποιούνται τόσο στη διάγνωση όσο και στη θεραπεία [33,34]. Ως διαγνωστικοί παράγοντες χρησιμοποιούνται ραδιοϊσότοπα που εκπέμπουν ακτινοβολία γ, όπως τα 67 Ga, 111 In, 99m Tc, 201 Tl για την τεχνική SPECT (Single-Photon Emission Computed Tomography) ή ραδιοϊσότοπα που εκπέμπουν ακτίνες β+ (ποσιτρόνια), όπως τα 55 Co, 64 Cu, 66 Ga, 68 Ga, 82 Rb, 86 Y για την τεχνική PET (Positron Emission Tomography) [35,36]. [39].…”

Section: To 2-(4΄-αμινοφαινυλο)βενζοθειαζόλιοunclassified

Σύνθεση Και Χαρακτηρισμός Συμπλόκων Στοιχείων Μεταπτώσεως Με Παράγωγα Του Βενζοθειαζολίου

Μαυροειδή¹

View full text Add to dashboard Cite

Στην παρούσα διδακτορική διατριβή συνετέθησαν δύο υποκαταστάτες που φέρουν την αντικαρκινική ομάδα του 2-(4΄-αμινοφαινυλο)βενζοθειαζολίου συνδεδεμένη, μέσω ανθρακικής αλυσίδας, με την 2-αμινομεθυλοπυριδίνη. Τα ανωτέρω συμπλέχθηκαν επιτυχώς με Pd(II), Pt(II) και Cu(II) και ακολούθησε χαρακτηρισμός των υποκαταστατών και των συμπλόκων με διάφορες φασματοσκοπικές μεθόδους (IR, NMR, MS, UV-Vis και EPR). Σε συνέχεια της μελέτης, πραγματοποιήθηκε η διερεύνηση της αλληλεπίδρασης των ενώσεων με το CT-DNA, με τη χρήση του κυκλικού διχρωϊσμού (CD),φασματοσκοπίας υπεριώδους-ορατού (UV-Vis), φθορισμού, ιξωδομετρίας και μελετών θερμικής μετουσίωσης. Τα αποτελέσματα ανέδειξαν την ικανότητατων υποκαταστατών αλλά και των αντίστοιχων συμπλόκων να αλληλεπιδρούν ισχυρά με το DNA. Ο συνεργιστικός τρόπος δράσης των υπό μελέτη ενώσεων περιλαμβάνει αλληλεπίδραση μέσω δέσμευσης στις αύλακες τουDNA και μη κλασσικής παρεμβολής και, ενώ επιπροσθέτως για τα σύμπλοκα προτείνεται και ομοιοπολική αλληλεπίδραση των μετάλλων με το DNA.Τέλος, αξιολογήθηκε η in vitro βιολογική τους δράση, σε δυο ανθρώπινες καρκινικές κυτταρικές σειρές μαστού (MCF-7 και ΜDA-MB-231) και στη φυσιολογική ανθρώπινη σειρά ινοβλαστών δέρματος DSF. Τα πρoκαταρκτικά βιολογικά αποτελέσματα είναι ιδιαιτέρως ενθαρρυντικά αφού διαπιστώθηκε εκλεκτική κυτταρική πρόσληψη και αυξημένη κυτταροτοξική δράση των υπό μελέτη ενώσεων στις δοκιμαζόμενες καρκινικές κυτταρικές σειρές μαστού.

show abstract

Design, synthesis and SAR studies of novel 1,2-bis(aminomethyl)cyclohexane platinum(II) complexes with cytotoxic activity. Studies of interaction with DNA of iodinated seven-membered 1,4-diaminoplatinocycles

Cited by 16 publications

References 50 publications

Molecular Evolution of the Oxygen-Binding Hemerythrin Domain

Molecular Evolution of the Oxygen-Binding Hemerythrin Domain

Glucosamine-Modified Reduction-Responsive Polymeric Micelles for Liver Cancer Therapy

Σύνθεση Και Χαρακτηρισμός Συμπλόκων Στοιχείων Μεταπτώσεως Με Παράγωγα Του Βενζοθειαζολίου

Contact Info

Product

Resources

About